Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8DJTO7)

• DOT Name: U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10)
• Synonyms: M phase phosphoprotein 10
• Gene Name: MPHOSPH10
• Related Disease:
  Breast cancer
  Breast carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Pulmonary emphysema
• UniProt ID: MPP10_HUMAN
• PDB ID: 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF04006
• Sequence:
  MAPQVWRRRTLERCLTEVGKATGRPECFLTIQEGLASKFTSLTKVLYDFNKILENGRIHG
  SPLQKLVIENFDDEQIWQQLELQNEPILQYFQNAVSETINDEDISLLPESEEQEREEDGS
  EIEADDKEDLEDLEEEEVSDMGNDDPEMGERAENSSKSDLRKSPVFSDEDSDLDFDISKL
  EQQSKVQNKGQGKPREKSIVDDKFFKLSEMEAYLENIEKEEERKDDNDEEEEDIDFFEDI
  DSDEDEGGLFGSKKLKSGKSSRNLKYKDFFDPVESDEDITNVHDDELDSNKEDDEIAEEE
  AEELSISETDEDDDLQENEDNKQHKESLKRVTFALPDDAETEDTGVLNVKKNSDEVKSSF
  EKRQEKMNEKIASLEKELLEKKPWQLQGEVTAQKRPENSLLEETLHFDHAVRMAPVITEE
  TTLQLEDIIKQRIRDQAWDDVVRKEKPKEDAYEYKKRLTLDHEKSKLSLAEIYEQEYIKL
  NQQKTAEEENPEHVEIQKMMDSLFLKLDALSNFHFIPKPPVPEIKVVSNLPAITMEEVAP
  VSVSDAALLAPEEIKEKNKAGDIKTAAEKTATDKKRERRKKKYQKRMKIKEKEKRRKLLE
  KSSVDQAGKYSKTVASEKLKQLTKTGKASFIKDEGKDKALKSSQAFFSKLQDQVKMQIND
  AKKTEKKKKKRQDISVHKLKL
• Function: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[2]
Pulmonary emphysema	DIS5M7HZ	Limited	Biomarker	[3]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[14]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of U3 small nucleolar ribonucleoprotein protein MPP10 (MPHOSPH10).	[13]

References

• [1] Mutant Bik expression mediated by the enhanced minimal topoisomerase IIalpha promoter selectively suppressed breast tumors in an animal model.Cancer Gene Ther. 2006 Jul;13(7):706-19. doi: 10.1038/sj.cgt.7700945. Epub 2006 Mar 3.
• [2] Sympathetic Hyperactivity and Sleep Disorders in Individuals With Type 2 Diabetes.Front Endocrinol (Lausanne). 2019 Nov 1;10:752. doi: 10.3389/fendo.2019.00752. eCollection 2019.
• [3] The 6-Minute Walk Test as a Tool for Determining Exercise Capacity and Prognosis in Patients with Silicosis.Arch Bronconeumol (Engl Ed). 2019 Feb;55(2):88-92. doi: 10.1016/j.arbres.2018.07.004. Epub 2018 Aug 9.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.